Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella.
Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella.
复制标题
盘绕线圈稳定性与动力学之间的平衡可以调节BORDETELLA中BVGS传感器激酶的活性。
DOI：
10.1128/mbio.02089-15
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发表时间：
2016-03-01
期刊：
影响因子：
6.4
通讯作者：
Jacob-Dubuisson F
中科院分区：
文献类型：
--
作者：
Lesne E;Krammer EM;Dupre E;Locht C;Lensink MF;Antoine R;Jacob-Dubuisson F
双组分系统BvgAS控制百日咳杆菌毒力调节子的表达。BvgS是具有细胞质外捕蝇草感知域的细菌传感器激酶的原型。在其跨膜片段之后，BvgS具有胞质Per-Arnt-Sim（PAS）结构域，然后是预测的2-螺旋卷曲螺旋，其先于激酶的二聚化-组氨酸-磷酸转移结构域。BvgS同源物具有类似的结构域组织，或者它们在跨膜和二聚化组氨酸磷酸转移结构域之间仅具有预测的卷曲螺旋。在这里，我们表明，2-螺旋卷曲螺旋的BvgS调节的酶活性的机械方式。它的边缘稳定的疏水界面，使一个伟大的旋转动力学的状态之间的开关在激酶模式和更刚性的构象在磷酸酶模式响应于信号感知的周质结构域。我们进一步表明，如果BvgS的PAS结构域被替换为PAS-少同源物的天然α-螺旋序列，则BvgS的活性以相同的方式受到控制。捕蝇草领域的蛤壳运动触发了卷曲线圈的动态变化。因此，我们已经发现了一个一般的机制，为BvgS家庭的金星捕蝇草含有双组分传感器激酶的监管。百日咳病原体百日咳博德特氏菌的双组分系统BvgAS以协调的方式调节感染所必需的毒力因子。BvgS是在主要细菌病原体中发现的传感器激酶蛋白家族的原型。当BvgS作为激酶发挥作用时，B.百日咳是有毒的，并且在BvgS感测到使其切换为磷酸酶的化学物质之后，细菌转变为无毒相。我们的目标是破译BvgS的信号传导机制，以了解博德特氏菌的毒力调控，这可能会导致针对这些双组分系统的新的抗菌治疗。我们发现BvgS的活性以机械方式调节。在酶结构域之前的蛋白质的短区域响应于其他BvgS结构域的信号感知而在两种状态之间切换。这个开关区域在BvgS同源物中是保守的，因此，这里揭示的调控可能与该家族相关。
The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases. The two-component system BvgAS of the whooping cough agent Bordetella pertussis regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase, B. pertussis is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in Bordetella, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.